Persistent Pulmonary Arterial Hypertension Research Articles

Contemporary survival outcomes of congenital systemic-to-pulmonary shunt in children with borderline pulmonary vascular resistant index compared to Eisenmenger syndrome

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) is a complication that occurs after unrepaired significant systemic-to-pulmonary shunt. Treatment options for PAH-CHD-predominantly left-to-right (L-R) shunt in children with borderline-high pulmonary vascular resistant index (PVRi) have been debated. We aimed to assess the treatment and survival of children with PAH-CHD-predominantly L-R shunt with borderline to high PVRi, using Eisenmenger syndrome (ES) for comparison. In 1995–2021, a total of 142 patients with ES and 192 children with PAH-CHD-predominantly L-R shunt were eligible for our analysis. The PVRi in ES patients was 26.7 ± 16.8 WU m2. Most patients (91%) received PAH-targeted therapy. Of the 192 children with PAH-CHD-predominantly L-R shunt, the baseline PVRi was 9.2 ± 5.8 WU m2. A total of 64 patients (33.3%) had borderline PVRi (4–8 WU m2) and 98 patients (51%) had high PVRi (> 8 WU m2). Most patients (88.5%) responded to acute pulmonary vasodilatory testing and underwent repair, with 158 undergoing defect closure and 12 having fenestrated closure. A treat-and-repair strategy was used in 33 children (17.1%). The 10- and 15-year survival rates for patients with ES were 79.3% and 72.4%, respectively, which was significantly inferior to children with borderline PVRi [97.3% and 87.8% (p = 0.02)]; and high PVRi [91.6% and 89.5% (p = 0.06)], respectively. The survival rate of children receiving treat-and-repair was slightly higher than that of ES (p = 0.16). The independent mortality risk in children with PAH-CHD-predominantly L-R shunt was persistent PAH following the defect correction (adjusted hazard ratio 5.8, 95% CI 1.7–19.9, p = 0.005).Trial registration: TCTR20200420004.

Impact of long lasting pulmonary arterial hypertension on the surgery of congenital heart defect

BackgroundLittle is known about the management of this high-risk subgroup of patients because only a few small retrospective studies were available in the literature. ObjectivesThis study was designed to identify the determinants of post operative mortality and to assess during 10 years follow-up functional and hemodynamic variables for children presenting at surgery with pulmonary vascular disease associated with congenital heart defect. MethodsThis is a prospective study that enrolled children with pulmonary arterial hypertension associated with congenital heart disease and presenting beyond the optimal time frame for surgery. Inclusion criteria were late presentation for surgery and severe pulmonary arterial hypertension, defined as mean pulmonary arterial pressure > 50 mmhg. An univariable analysis, receiver operating characteristic curves, and Kaplan-Meier curves were used for survival analysis. Results75 patients underwent repair of their cardiac lesions. The operative mortality rate was 16%(12 patients); 43 patients (57 %) had right heart catheterization, and all of them were positive for acute vasodilatatory challenge (NO, oxygen). In the postoperative period, 32 % of patients had pulmonary hypertensive crisis, and 72 % had right heart failure. During follow-up, pulmonary arterial hypertension subclass 4 was present in 5% of our patients. ConclusionOur study indicated that for operable patients but beyond the optimal time frame the surgical mortality remained high despite using iNO. However, for those who survived they achieved good results in functional exercise, their PAP dropped to normal level and small proportion had persistent pulmonary arterial hypertension encouraging surgical closure of the defect.

Analysis of Patients with Severe ARDS on VV ECMO Treated with Inhaled NO: A Retrospective Observational Study.

(1) Background: This retrospective study focused on severe acute respiratory distress syndrome (ARDS) patients treated with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) and who inhaled nitric oxide (NO) for pulmonary arterial hypertension (PAH) and/or right ventricular failure (RV failure). (2) Methods: Out of 662 ECMO-supported patients, 366 received VV ECMO, including 48 who inhaled NO. We examined the NO's indications, dosing, duration, and the ability to lower PAH. We compared patients with and without inhaled NO in terms of mechanical ventilation duration, ECMO weaning, organ dysfunction, in-hospital mortality, and survival. (3) Results: Patients received 14.5 ± 5.5 ppm NO for 3 days with only one-third experiencing decreased pulmonary arterial pressure. They spent more time on VV ECMO, had a higher ECMO weaning failure frequency, and elevated severity scores (SAPS II and TIPS). A Kaplan-Meier analysis revealed reduced survival in the NO group. Multiple variable logistic regression indicated a twofold increased risk of death for ARDS patients on VV ECMO with NO. We observed no increase in continuous renal replacement therapy. (4) Conclusions: This study suggests that persistent PAH and/or RV failure is associated with poorer outcomes in severe ARDS patients on VV-ECMO, with an inhaled NO responder rate of only 30%, and it does not impact acute kidney failure rates.

Transcatheter Management of Pulmonary Sequestrations in Children-A Single-Center Experience.

A pulmonary sequestration (PS) is an area of bronchopulmonary tissue with aberrant arterial supply. Transcatheter occlusion of PSs is an appealing treatment option, but data on outcomes remain scarce. We aim to describe our experience with transcatheter management of PS in infants and children. Retrospective review of clinical data of all patients with suspected PS sent for diagnostic and/or interventional cardiac catheterization at our institution between January 1999 and May 2021. Procedural considerations, techniques, standard safety, and outcomes were assessed. We identified 71 patients (52.1% males), with median age and weight of 4.9 months (IQR, 2.1-26.6) and 4.2 kg (IQR, 3.9-12.1), respectively. Sixty-one (86%) patients had associated congenital heart defects (CHDs). Forty-two (59%) patients had pulmonary arterial hypertension (PAH) at the time of diagnosis. Fifty-three (74.7%) patients underwent embolization of the PS feeding vessel using microcoils and/or vascular plugs, and eight (15.1%) of these were neonates who presented with severe PAH and cardiac failure. Two patients had large feeding vessels and were treated surgically. Sixteen (22.5%) patients with small feeding vessels received conservative management. At median follow-up of 36.4 months (IQR, 2.1-89.9), seven patients had died, 24 patients had CHD corrective surgeries, 26 patients had redo catheterizations, and five patients had persistent PAH. No PS surgical resection was needed, and no infection of the remaining lung tissue occurred. Transcatheter assessment and treatment of PSs is a safe and effective procedure. Neonates with large PSs are severely symptomatic and improve remarkably after PS closure. PS embolization and surgical repair of associated CHDs generally leads to the normalization of pulmonary pressures.

Use of Perioperative Extracorporeal Membranous Oxygenation in Pulmonary Endarterectomy Cases: A Systematic Review and Meta-Analysis.

Introduction: Pulmonary endarterectomy (PEA) is known to be a curative intervention for chronic thromboembolic pulmonary hypertension (CTEPH). Its complications include endobronchial bleeding, persistent pulmonary arterial hypertension, right ventricular failure, and reperfusion lung injury. Extracorporeal membranous oxygenation (ECMO) is a perioperative salvage method for PEA. Although risk factors and outcomes have been reported in several studies, overall trends remain unknown. We performed a systematic review and study-level meta-analysis to understand the outcomes of ECMO utilization in the perioperative period of PEA. Methods: We performed a literature search with PubMed and EMBASE on 11/18/2022. We included studies including patients who underwent perioperative ECMO in PEA. We collected data including baseline demographics, hemodynamic measurements, and outcomes such as mortality and weaning of ECMO and performed a study-level meta-analysis. Results: Eleven studies with 2632 patients were included in our review. ECMO insertion rate was 8.7% (225/2,625, 95% CI 5.9-12.5) in total, VV-ECMO was performed as the initial intervention in 1.1% (41/2,625, 95% CI 0.4-1.7) (Figure 3), and VA-ECMO was performed as an initial intervention in 7.1% (184/2,625, 95% CI 4.7-9.9). Preoperative hemodynamic measurements showed higher pulmonary vascular resistance, mean pulmonary arterial pressure, and lower cardiac output in the ECMO group. Mortality rates were 2.8% (32/1238, 95% CI: 1.7-4.5) in the non-ECMO group and 43.5% (115/225, 95% CI: 30.8-56.2) in the ECMO group. The proportion of patients with successful weaning of ECMO was 72.6% (111/188, 95% CI: 53.4-91.7). Regarding complications of ECMO, the incidence of bleeding and multi-organ failure were 12.2% (16/79, 95% CI: 13.0-34.8) and 16.5% (15/99, 95% CI: 9.1-28.1), respectively. Conclusion: Our systematic review showed a higher baseline cardiopulmonary risk in patients with perioperative ECMO in PEA, and its insertion rate was 8.7%. Further studies that compare the use of ECMO in high-risk patients who undergo PEA are anticipated.

Echocardiographic evaluation of right heart pressure changes in healthy newborns and its follow-up till 12 weeks of life

Background: Right ventricular (RV) pressure undergoes a series of changes from foetal to neonatal period on both left and right heart. Pulmonary velocity acceleration time (PVAccT) measured by trans-thoracic echocardiography has been established as a reliable indicator of RV pressure measurement in neonates. This study aims to throw some light into the changes in the RV pressure by serial PVAccT measurements in the initial 12 weeks of life. Materials and Methods: A cross sectional study was carried out among term new-borns until 12 weeks of age and serial changes in the PVAccT values were recorded, reflecting the mean pulmonary artery pressure (MPAP), and the left ventricular internal diastolic diameter (LVIDD), left atrial diameter (LAD), right ventricular outflow tract (RVOT), right ventricular free wall thickness (RVFWT). Results: There was gradual increase in the mean value of PVAccT with age from birth i.e., 1-3 days (70.08±18.62ms) to 3 months (86.23±17.31ms) (p=<0.05). Mean value of right ventricular outflow tract proximal diameter was also seen to have an increase from day 1-3 (0.92±0.19cm) to 3 months of age (1.09±0.01cm) (p= <0.001). There was an overall decrease in the mean value of the RVFWT from day 1-3 (0.37±.07 cm) to 3 months (0.27±0.07cm) of age after an increase at 1 month (p=<0.05). Statistically significant increase in mean LAD from 1.18±0.29cm to 1.40±0.35 cm and LVIDD from 1.54±0.31cm to1.96±0.27 was seen from birth to 3 months of age. Conclusion: Changes in PVAcct and RV pressure with time from birth to 3 months of age will aid in early diagnosis of persistent pulmonary artery hypertension of new-born (PPHN) or pulmonary arterial hypertension (PAH).

Abstract 9727: Reduced Bmpr2 Causes a Decrease in Foxf1 That Links Unrepaired DNA Damage to Persistent Pulmonary Hypertension

Introduction: B MPR2 mutation is the most common genetic cause of pulmonary arterial hypertension (PAH). Loss of BMPR2 causes pulmonary arterial (PA) endothelial cell (EC) dysfunction and impairs EC-mediated suppression of smooth muscle cells proliferation. These are characteristic features of PAH vascular cells as is the presence of DNA damage that can be induced by oxidative stress. We previously showed that EC- Bmpr2 -/- mice have persistent pulmonary hypertension (PH) with reoxygenation after hypoxia. However, the role of DNA damage in causing persistent PH related to loss of BMPR2 and oxidative stress is unknown. Hypothesis: We hypothesize that loss of BMPR2 causes unrepaired DNA damage and persistent PH by altering the expression of genes that maintain EC homeostasis. Methods and Results: DNA damage assessed by γH2AX foci was observed in PAEC of EC- Bmpr2 -/- mice in room air, that was more extensive after reoxygenation (10% hypoxia for 3 weeks followed by recovery in room-air for 4 weeks). Deletion of the DNA damage sensor ataxia-telangiectasia mutated (ATM) in EC of mice (EC- Atm -/- ) also resulted in persistent DNA damage and PH. RNA sequencing of PAEC after reoxygenation in EC- Bmpr2 -/- and EC- Atm -/- mice vs. controls showed downregulated EC differentiation and development genes enriched in biding motifs for Foxf1, a transcription factor associated with DNA repair and angiogenesis. Foxf1 expression was reduced in PAEC with loss of BMPR2 or ATM. Loss of Foxf1 decreased angiogenic genes Cldn5 and Vegfr2 , and DNA damage response genes Atm and p53 , and impaired PAEC migration and tube formation. Foxf1 overexpression increased these genes in PAEC. Immunohistochemistry showed decreased FOXF1 in PAEC of human pulmonary vascular lesions. Delivery of Foxf1 to EC- Bmpr2 -/- mice with an AAV2-peptide targeting the PA endothelium attenuated DNA damage in PAEC, restored angiogenesis genes and completely reversed persistent PH returning right ventricular systolic pressure to normal levels. Conclusions: We link loss of BMPR2 and DNA damage sensing in PAEC to persistent DNA damage and PAH and show that both are mediated by reduced FOXF1 . In EC- Bmpr2 -/- mice, Foxf1 gene therapy attenuated DNA damage restored angiogenesis genes, and prevented persistent PH.

Comparison of the Effectiveness of Bosentan and Sildenafil in the Management of Persistent Pulmonary Arterial Hypertension in Neonates

Comparison of the Effectiveness of Bosentan and Sildenafil in the Management of Persistent Pulmonary Arterial Hypertension in Neonates

Prediction score for prolonged hospital stay in meconium aspiration syndrome: A multicentric collaborative cohort of south India.

With improved survival in neonates with meconium aspiration syndrome (MAS), the focus is currently on mitigating the morbidities. The objective of this study was to predict factors determining prolonged hospital stay in neonates with MAS. It was a retrospective cohort from five centers of south India between 2018 and 2020. Neonates ≥35 weeks of gestation admitted to neonatal intensive care unitwith the diagnosis of MAS and requiring oxygen beyond 24 h of life were included in the study. The morbidities in the neonates with stay ≤7 days (short stay) were compared with >7 days (prolonged stay). Logistic regression by the backward stepwise method was used for predictive score creation. Out of 347 neonates with MAS discharged home, 103 (29%) had a short stay and 244 (71%) had prolonged stay. The primary support beyond O2 (continuous positive airway pressure/mechanical ventilation) (42% vs. 83%, p < 0.001), fractional inspired oxygen (FiO2 ) at 1 h >30% (45% vs. 87%, p < 0.001), hypoxic ischemic encephalopathy(HIE) stage2 or 3 (1% vs. 27%, p < 0.001), moderate-severe persistent pulmonary artery hypertension(PPHN) (3% vs. 31%, p < 0.001) were independent factors associated with prolonged stay on logistic regression. A prediction model was devised using weighted scores of these four associated morbidities. The clinical score thus developed had 83% sensitivity, 68% specificity for the prediction of prolonged stay (area under curve:82%, 95% confidence interval [78-87], p < 0.001). More than two-thirds of neonates with MAS had prolonged stay. The primary support beyond oxygen, FiO2 requirement >30%, Moderate to severe PPHN, HIE stage2 or 3 were predictive of prolonged stay in neonates with MAS.

A Morphomolecular Approach to Alveolar Capillary Dysplasia

Alveolar capillary dysplasia (ACD) is a rare lung developmental disorder leading to persistent pulmonary arterial hypertension and fatal outcomes in newborns. The current study analyzed the microvascular morphology and the underlying molecular background of ACD. One ACD group (n=7), one pulmonary arterial hypertension group (n=20), and one healthy con1trol group (n=16) were generated. Samples of histologically confirmed ACD were examined by exome sequencing and array-based comparative genomic hybridization. Vascular morphology was analyzed using scanning electron microscopy of microvascular corrosion casts. Gene expression and biological pathways were analyzed using two panels on inflammation/kinase-specific genes and a comparison analysis tool. Compartment-specific protein expression was analyzed using immunostaining. In ACD, there was an altered capillary network, a high prevalence of intussusceptive angiogenesis, and increased activity of C-X-C motif chemokine receptor 4 (CXCR4), hypoxia-inducible factor 1α (HIF1A), and angiopoietin signaling pathways compared with pulmonary arterial hypertension/healthy controls. Histologically, there was a markedly increased prevalence of endothelial tyrosine kinase receptor (TEK/TIE2)+macrophages in ACD, compared with the other groups, whereas the CXCR4 ligand CXCL12 and HIF1A showed high expression in all groups. ACD is characterized by dysfunctional capillaries and a high prevalence of intussusceptive angiogenesis. The results indicate that endothelial CXCR4, HIF1A, and angiopoietin signaling as well as TIE2+ macrophages are crucial for the induction of intussusceptive angiogenesis and vascular remodeling. Future studies should address the use of anti-angiogenic agents in ACD, where TIE2 appears as a promising target.

Valve patch technique for repair of ventricular septal defect: long-term results

This study aimed to show the long-term results in patients who underwent unidirectional valve patch repair of ventricular septal defect with pulmonary artery hypertension. Thirty-five acyanotic patients aged 2 to 26 years (mean 9.3 years) with a large ventricular septal defect and elevated pulmonary vascular resistance (mean 9.5 Wood units) underwent surgery in Madani Heart Hospital. The medical records and clinical outcomes were reviewed from March 1998 to March 2017. Five patients died in the first postoperative week. In the long-term follow-up (mean 11 years), two patients were lost to follow-up. Pulmonary artery hypertension gradually decreased in 17 patients within 6-12 months with significant improvement in right ventricular end-diastolic diameter, New York Heart Association functional class, and tricuspid regurgitation. Eleven patients with persistent pulmonary artery hypertension were divided into tolerable and non-tolerable groups. Six patients in the tolerable group had satisfactory conditions compared to before the operation, and gained weight with improved functional class despite echocardiographic findings of persistent elevated pulmonary artery pressure. One had a full-term delivery by caesarean section in the fifth postoperative year. Five patients in the non-tolerable group gradually developed right heart failure and complications such as extremity edema, ascites, pleural effusions, and died after 10-30 months. Although relatively high mortality occurred during long-term follow-up, surviving patients were in a better condition and functional class despite persistent pulmonary artery hypertension. Therefore, fear of persistent pulmonary artery hypertension should not prohibit surgery in this group of patients.

Management of Persistent Pulmonary Hypertension After Correction of Congenital Heart Defect with Autologous Marrow-Derived Mononuclear Stem Cell Injection into the Pulmonary Artery: A Pilot Study.

Pulmonary arterial hypertension (PAH) related to left-to-right shunt can progress to Eisenmenger syndrome, a serious and fatal disease that is not yet curable. This pilot study considered stem cell injection as a new treatment modality in persistent pulmonary hypertension after the correction of a congenital heart defect. Three patients with persistent pulmonary hypertension after ventricular septal defect repair were included in this pilot study for a clinical trial. Mononuclear stem cells derived from patients' bone marrow specimens were injected into the right and left pulmonary arteries via cardiac catheterization. The patients were followed over a 6-month period, with six-minute walk test, echocardiography and repeated angiography performed in the sixth month after treatment. The results of the study showed improvement of 40m, 280m and 100m in 6-minute walk distance in patients 1 to 3, respectively. The peak PR gradient decreased 2, 5 and 9mmHg by echocardiography, and mean PA pressure decreased 21, 22 and 9mmHg by catheterization in patients 1 to 3, respectively. Pulmonary artery resistance decreased 4, 4.5 and 1.3 Wood units after 6months of stem cell therapy in the three patients. No short-term complications were detected in this pilot trial, and all patients tolerated the procedure without any complications. Intrapulmonary artery injection of stem cells may have a role in the treatment of persistent PAH secondary to congenital heart disease. This procedure is feasible, with no significant complications, and this study can be considered as a platform for larger studies.

Comparison of the effects of bosentan and sildenafil in the treatment of persistent pulmonary arterial hypertension in infants

Background: Persistent pulmonary hypertension (PPHN) is a life-threatening condition in neonates. In developing countries, mortality is estimated to be around 10%–20% due to lack of access to the main drug, inhaled nitric oxide. Bosentan as an endothelin type A and B receptor antagonist and sildenafil as a phosphodiesterase inhibitor type 5 are effective in reducing pulmonary vascular resistance and pulmonary artery pressure (PAP). Materials and Methods: A double-blind clinical trial was conducted at the intensive care unit of Akbarabadi Hospital Tehran between October 2017 and September 2019. The efficacy, safety, and possible side effects of bosentan and sildenafil were evaluated in neonates suffering from PPHN. Echocardiographic findings, duration of oxygen dependency, invasive ventilation support requirement, duration of medication, short-term outcomes including blood pressure, white blood cell, and hemoglobin counts were compared between the two groups. Results: Bosentan is as effective as sildenafil in reducing PAP and improving cardiac output. The duration of treatment with bosentan was significantly shorter than that of sildenafil (P = 0.002). The time of oxygen demand was similar between both the groups, ranging from 15 to 17 days (P = 0.198). The need for invasive ventilation support was similar in both the groups (P = 0.989). Although PAP and the severity of tricuspid valve insufficiency were higher before treatment, the third echocardiographic findings such as pulmonic insufficiency (P = 0.194), tricuspid regurgitation (P = 0.368), and ejection fraction (P = 0.160) were similar in bosentan and sildenafil groups. The need for supportive inotropic drugs was similar in both the groups. There was no statistically significant difference in the mean of blood pressure, white blood cell, and hemoglobin counts between the two groups.Conclusion: Bosentan is effective in the treatment of PPHN in neonates and reduces it over a shorter period of time. It is more efficient in reducing PAP and decreases the severity of tricuspid valve insufficiency in a shorter time compared to sildenafil.

Pulmonary Arterial Hypertension (PAH) Is Associated with Increased Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplantation (allo HCT) for Myelofibrosis

Background AlloHCT is the only curative therapy for primary and secondary myelofibrosis (MF). Pulmonary arterial hypertension (PAH) can be seen in 30% of patients with MF. PAH can eventually lead to right heart failure and may be associated with complications after alloHCT. The primary objective was to determine the association of PAH with alloHCT outcome in patients with MF. Secondary objectives included the effect of HCT on the underlying PAH as well as incidence of specific transplant-related complications in these patients. Methods All patients with MF who underwent alloHCT from 2008 to early 2018 at the City of Hope Medical Center with evaluable pre-HCT echocardiography were considered for this retrospective analysis. Pre and postHCT echocardiograms were reviewed to evaluate the pulmonary arterial systolic pressure (PASP). Descriptive statistics were used for baseline patient and transplant related characteristics stratified by PAH. Paired t-test was used to detect the change in the pulmonary vascular pressure after HCT. Kaplan-Meier and cumulative incidence curves were constructed for OS and NRM), respectively. Log-rank test and Gray's test were used whenever appropriate. Results 65 patients with MF that met the inclusion criteria were studied. Median age at HCT was 61 years with 36 (55%) males. 39 (60%) patients had intermediate 2 or high DIPPS score at the time of HCT. 37 (57%) had JAK2 positive MF. . Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 out of 65 patients (57%) meeting the diagnostic criteria for PAH. With median follow-up of 35.0 months (range: 3.3 – 119.4), PAH was significantly associated with inferior OS (58.9% vs. 88.8%, p=0.025), primarily due to increased NRM (21.6% vs. 7.1%, p= 0.007). 57% of deaths (8 of 14) in patients with PAH occurred within day 100 after HCT. In patients with available post-HCT echocardiogram (n=33) eight patients (24%) had persistent PAH with the median pulmonary artery pressure of 30mmHg. Compared with pre-HCT values pulmonary arterial pressure was significantly reduced after HCT (p Conclusion PAH is associated with inferior survival due to increased NRM in patients with MF undergoing alloHCT. About half of deaths in patients with PAH occurred within 100 days of HCT. PAH appears at least partially reversible after successful alloHCT. Based on our data, PAH should be considered a risk factor for early mortality after alloHCT and surveillance of pulmonary artery pressure in MF patients being considered for alloHCT may be useful.

Évolution respiratoire à moyen et long terme des enfants opérés d’une hernie diaphragmatique congénitale : à partir d’une série de 56 patients

Recent advances in prenatal diagnosis, high frequency oscillatory ventilation and pulmonary arterial hypertension (PAH) therapies have progressively improved the survival of patients with congenital diaphragmatic hernia (CDH). However, CDH is associated with high morbidity that affects about half of surviving children. The main sequelae observed are respiratory (asthma, persistent PAH [PPAH], bronchopulmonary dysplasia, respiratory infections) and digestive (gastroesophageal reflux disease [GERD]). This retrospective study focuses on the medium and long-term respiratory evolution of a cohort of 56children with CDH and operated at Strasbourg University Hospital between 1999and 2017. The mean age at assessment was 6,6years (minimum: 5months; maximum: 19years). Seventeen patients (30%) had asthmatic manifestations. Pulmonary Function Tests (PFT) showed obstructive patterns in 5/11patients (2with post-bronchodilator reversibility), and restrictive impairment in 5/11patients, 3of whom had thoracic deformity and/or scoliosis. Thirteen patients (23%) had bronchopulmonary dysplasia. Few patients had recurrent respiratory infections (3.6%) and chronic respiratory insufficiency (5.3%). Thirty-nine patients (70%) presented with an initial PAH, two of whom progressed to PPAH. Sixteen patients (29%) had thoracic deformity and/or scoliosis and 48patients (86%) had GERD, 10of whom had fundoplication. The long-term respiratory outcome of CDH operated patients is characterized by a moderate prevalence of respiratory symptoms and alterations in PFT that are important to consider in their medical follow-up during adolescence and adulthood. PAH is common in the neonatal period but rarely seems to persist.

Clinical profile of persistent pulmonary hypertension in new born: experience in an extramural institution

Background: Persistent pulmonary artery hypertension of the new born (PPHN) has an incidence of 1.9 per 1000 live births with a mortality of 12 to 29%. In our tertiary care referral institute, the mortality was relatively high. A department audit was undertaken which will help us to introspect and to reason out the factors favouring survival and mortality in our NICU.Methods: Neonates with the diagnosis of PPHN from January 2016 to December 2016 were identified from our department database. After excluding cardiac causes of pulmonary hypertension, transport, prenatal, perinatal and post-natal data, treatment details and outcome information was collected from case records. The statistical analysis was calculated with SPSS software. Mean, standard deviation was calculated for continuous variables. Chi square test and Fischer’s exact test was used to test the association between categorical variables and t test for continuous variables.Results: The incidence PPHN in our unit was 1.5%. The average duration of hospital stay was 17 days. Among the 45.7 % of babies, PPHN was secondary to MAS, followed by CDH (22.3 %). Based on oxygenation index, 15 babies, 42.3% had mild, 10 babies, 28.6% had moderate, 8 babies, 22.3% had severe PPHN and 3 babies ,8.6% had severe PPHN. Overall mortality was 42.3%. SpO2 on arrival at emergency room, adequacy of cardiorespiratory during transport and presence of shock is significantly associated with mortality.Conclusions: This study show MAS and CDH are common causes of PPHN. Severity of illness at arrival was predictive of high mortality. Prior stabilization and adequate transport may improve outcomes.

Levoatrial cardinal vein with normal left ventricle: A forgotten cause of pulmonary arterial hypertension.

Levoatrial cardinal vein (LACV) is anomalous connection between left atrium or pulmonary veins and systemic veins such as innominate vein or superior vena cava. This persistence of splanchnic circulation occurs when there is left-sided obstructive cardiac lesions such as hypoplastic left heart or mitral atresia. In this report we present three cases of LACV with well-developed left heart, without any obstructive lesions. All our cases presented with pulmonary arterial hypertension (PAH) and had associated intracardiac shunt such as ventricular/atrial septal defect and supracardiac partial anomalous pulmonary venous connection. Apart from the above shunts, LACV contributed to PAH in these cases. It is important to detect and report LACV as this may require surgical correction along with other defects. If LACV goes undetected during imaging workup, it may cause persistent PAH postoperatively.

Pulmonary arterial hypertension induced by tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of several neoplastic conditions; however, pulmonary arterial hypertension (PAH) has been reported as a complication of TKIs, predominantly with dasatinib. Recent studies have elucidated the potential mechanisms of TKI-induced PAH and have better clarified the long-term outcomes. In addition to the known association between dasatinib and PAH, several other TKIs have recently been reported to cause PAH, including ponatinib, bosutinib and lapatinib. Dasatinib causes direct pulmonary artery endothelial cell toxicity through the production of mitochondrial reactive oxygen species, but likely requires the presence of a second risk factor to cause PAH. Symptoms and haemodynamic abnormalities frequently resolve after discontinuation of the TKI, but PAH persists in over a third of patients and can reoccur when other TKIs are used, which warrants close follow-up. Rare fatal cases have occurred; therefore, treatment with PAH-specific therapy is recommended for patients with right heart failure or persistent PAH after discontinuation of the TKI. PAH is a rare but important complication of several TKIs. Management includes discontinuation of the TKI, close follow-up and PAH-specific therapy in severe cases.

Hemodynamic Evaluation of Children with Persistent or Recurrent Pulmonary Arterial Hypertension Following Complete Repair of Congenital Heart Disease.

Persistent or recurrent pulmonary arterial hypertension (PAH) following complete surgical repair of congenital heart disease (CHD) represents one of the largest group of PAH associated with CHD (PAH-CHD) in recent registry studies and seems to have a particularly poor prognosis. However, little is known about this fourth clinical subclass of PAH-CHD, especially in children. The purpose of this study was to assess specific characteristics of invasive hemodynamics of this disease in children, including acute vasodilator testing (AVT) and pulmonary endothelial function (PEF) and to compare to patients with idiopathic PAH (IPAH), who usually present with a similar fatal clinical course. Thirty-two children with PAH were included in the study, twelve of these patients had PAH-CHD subclass 4 (mean age 8.0±3.4years) and twenty children had IPAH (mean age 8.6±4.4years). Cardiac catheterization was performed in all children, including AVT and PEF. PEF was assessed by changes in pulmonary blood flow in response to acetylcholine (Ach) using Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. At baseline, the ratio of mean PA pressure to mean systemic arterial pressure (mPAP/mSAP) was comparably high in both groups (0.78±0.32 vs. 0.80±0.22), while the indexed pulmonary vascular resistance (PVRI) was significantly lower in the PAH-CHD group (12.6±6.8WUxm2) compared to IPAH patients (19.9±10.6WUxm2) (p=0.04). Cardiac index was significantly higher in the PAH-CHD group (4.19±1.09l/min/m2 vs. 3.23±0.76) (p=0.017). However, AVT revealed a significantly larger maximum response (percentage of fall of PVR/SVR ratio during AVT) in the IPAH group (37±22%) compared to the PAH-CHD group (13±23%) (p=0.017). PEF showed no significant difference between both patient groups (PFR 1.69±0.71 vs. 1.73±0.68) (p=0.76). Our study demonstrates significant pulmonary vascular disease in children with persistent or recurrent PAH following complete surgical repair of CHD similar to IPAH patients. Although baseline measures appeared to be more favorable, pulmonary vasoreactivity was markedly impaired in PAH-CHD subclass 4, which may contribute to its negative impact on the long-term outcome of this patient group.

Effect of prosthesis patient mismatch in mitral position on pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is associated with poor outcome after mitral valve replacement (MVR). We proposed to evaluate the effect of valve prosthesis patient mismatch (PPM) on pulmonary arterial (PA) pressure following MVR. Five hundred patients who have undergone MVR were studied retrospectively. Postoperative PA systolic pressure (PASP) measured 6 months postoperatively by Doppler echocardiography was compared with preoperative values. PASP ≥ 40 mmHg was defined as PAH. Mitral valve effective orifice area was calculated by the continuity equation and indexed for body surface area. PPM was defined as indexed effective orifice area ≤ 1.2 cm2/m2. A multivariate model was constructed to ascertain the independent determinants of systolic PA pressure. Also, a propensity score model was constructed to overcome the baseline differences between the PPM and no PPM groups. The incidence of PPM in this study was 37.2%. The average postoperative PASPs were 30.49 and 42.35 mmHg in the no PPM and PPM groups, respectively; (P < 0.001). Regression of PAH in the PPM and no PPM groups was 76.26% and 20.64%, respectively; (P < 0.001). The indexed effective orifice area correlated well with postoperative PASP (r = 0.71). The overall survival and freedom from cardiac death at 10 years were 79.8% and 85.3%; and at 20 years were 66.5% and 74.3%, respectively. Both, overall survival and the freedom from cardiac death were higher in the no PPM group than in the PPM group; (P < 0.001). Propensity score matching analysis yielded 112 pairs of the PPM and no PPM cohorts, which revealed higher overall survival and freedom from cardiac death in the no PPM group; (P = 0.028 and 0.012, respectively). Mitral PPM is an independent predictor of persistent PAH after MVR along with associated morbidity and reduced survival.